A consensus integrated care pathway for patients with primary biliary cholangitis: a guideline-based approach to clinical care of patients.

INTRODUCTION: Primary biliary cholangitis (PBC) is an infrequent, immune-mediated cholestatic liver disease, which can lead to liver fibrosis, cirrhosis and complications of end-stage liver disease. The established goals of treatment of PBC are prevention of end-stage liver disease and amelioration of associated symptoms. The European Association for the Study of the Liver (EASL) management guidelines provide extensive recommendations on the diagnosis and management of PBC. AREAS COVERED: This article describes the development by expert consensus of a 'PBC Integrated Patient Care Pathway' to simplify and standardize the management of PBC for clinicians based on current practice. EXPERT OPINION: Guideline adoption is potentially poor in practice since most patients with PBC in the community are seen by general gastroenterologists or hepatologists without a special interest in autoimmune liver disease. The PBC Integrated Patient Care Pathway is a best practice tool for clinicians designed to complement the EASL Clinical Practice Guidelines for the diagnosis and management of PBC patients. It gives clinicians a practical decision tree of the key steps in PBC management, thereby providing a simplified framework and an opportunity for more uniform practice that supports the safe and timely adoption of varied models of care provision to patients with PBC.

Treatment of primary biliary cirrhosis with ursodeoxycholic acid combined with traditional Chinese medicine: A protocol for systematic review and meta analysis.

OBJECTIVE: Ursodeoxycholic acid is the priority drug of primary biliary cirrhosis (PBC) and is usually combined with traditional Chinese medicine. This study aimed to systematically evaluate the benefits of integrated Chinese and western interventions for PBC. METHODS: Searched the randomized controlled trials in PubMed, Web of Science, CNKI, CBM, Wanfang, VIP databases. The Cochrane risk of bias tool was used for methodological quality assessment and all data analysis was performed using Revman5.3 and Stata14.2 software. RESULT: 30 randomized controlled trials involving 10 interventions with a total of 1948 participants were included. Identified the direct and indirect evidence of trials, and used network meta analyses ranked the benefits of different interventions based on pairwise meta analysis. The primary outcom was clinical efficacy rate. Secondary outcome was liver function, including alkaline phosphataseand total bilirubin. CONCLUSION: The conclusion of this systematic review provide credible evidence - based for the relative advantages of integrated Chinese and western interventions for PBC.

Transcutaneous Neuromodulation improved inflammation and sympathovagal ratio in patients with primary biliary ssscholangitis and inadequate response to Ursodeoxycholic acid: a pilot study.

BACKGROUND: At present, ursodeoxycholic acid (UDCA) is internationally recognized as a therapeutic drug in clinic. However, about 40% Primary Biliary Cholangitis (PBC) patients are poor responders to UDCA. It has been demonstrated that Transcutaneous Neuromodulation (TN) can be involved in gut motility, metabolism of bile acids, immune inflammation, and autonomic nerve. Therefore, this study aimed to explore the effect of TN combined with UDCA on PBC and related mechanisms. METHODS: According to inclusion and exclusion criteria, 10 healthy volunteers and 15 PBC patients were recruited to control group and TN group, respectively. PBC patients were alternately but blindly assigned to group A (TN combined with UDCA) and group B (sham-TN combined with UDCA), and a crossover design was used. The TN treatment was performed via the posterior tibial nerve and acupoint ST36 (Zusanli) 1 h twice/day for 2 weeks. T test and nonparametric test were used to analyze the data. RESULTS: 1. TN combined with UDCA improved the liver function of PBC patients shown by a significant decrease of alkaline phosphatase and gamma-glutamyltransferase (γ-GT) (P < 0.05). 2. The treatment also decreased serum IL-6 levels (P < 0.05), but not the level of Tumor Necrosis Factor-α, IL-1ß or IL-10. 3. TN combined with UDCA regulated autonomic function, enhanced vagal activity, and decreased the sympathovagal ratio assessed by the spectral analysis of heart rate variability (P < 0.05). 4. There was no change in 13 bile acids in serum or stool after TN or sham-TN. CONCLUSIONS: TN cssombined with UDCA can significantly improve the liver function of PBC patients. It is possibly via the cholinergic anti-inflammatory pathway. TN might be a new non-drug therapy for PBC. Further studies are required. TRIAL REGISTRATION: The study protocol was registered in Chinese Clinical Trial Registry (number ChiCTR1800014633 ) on 25 January 2018.

Diagnosis and treatment of primary biliary cholangitis.

Primary biliary cholangitis is a cholestatic, chronic autoimmune liver disease with a wide individual variation in disease progression. The diagnosis is predominantly based on chronic elevation of alkaline phosphatase and the presence of anti-mitochondrial antibodies or other specific antinuclear antibodies (i.e. anti-gp210 and anti-sp100). Even in early-stage disease, health-related quality of life can be severely impaired by symptoms such as pruritus, fatigue, and sicca syndrome and metabolic bone disease should be assessed and treated. The prognosis of the disease is, however, largely determined by the development of cirrhosis and its complications. Ursodeoxycholic acid is associated with an improved prognosis and should be initiated and continued in all patients. Clinical outcome is related to the biochemical response to ursodeoxycholic acid, but the prognosis of those with an incomplete response is still better than those who remain untreated. Obeticholic acid was recently approved as second-line treatment and bezafibrate may serve as an adequate off-label alternative, particularly in patients with pruritus. Preliminary data suggest an additive effect of triple therapy with ursodeoxycholic acid, obeticholic acid, and bezafibrate, whereas other promising drugs are being evaluated in clinical trials.

[Risk factors and therapeutic strategies for primary biliary cholangitis patients with poor prognosis].

With the progress in detection methods and the update of diagnostic and therapeutic concepts, more and more patients with primary biliary cholangitis (PBC) have been diagnosed and treated. A high proportion of PBC patients, however, progress to liver decompensation, with an increased risk of liver transplantation and death and a significant reduction in long-term survival. These patients need early diagnosis and urgent treatment. This article discusses how to identify the PBC patients with poor prognosis early from the aspects of biochemical response, disease features, and biomarkers, and reviews the progress in related complementary therapies and new drugs including Ocaliva, Fibrates, UDCA-derived drugs, and molecular targeted drugs.

Primary biliary cholangitis in China.

PURPOSE OF REVIEW: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by immunomediated destruction of small and medium-sized intrahepatic bile ducts. In 1987, a cDNA for a 74 kDa mitochondrial autoantigen was cloned and identified as the E2 component of the mitochondrial pyruvate dehydrogenase complex, which improved the diagnosis and changed research directions in this field. In 1958, the first Chinese case of PBC was reported. But until 1990, a comprehensive description of the characteristics of Chinese PBC patients was published. In China we now know that PBC is not rare and usually does not progress to cirrhosis. RECENT FINDINGS: The number of Chinese patients with PBC has increased each and every year. This increase may be associated with the changes of liver disease spectrum, the application of convenient autoantibody detection kits, and the comprehensive understanding of the disease. It may also reflect, however, a westernization change in environmental features with China. There is now significant and important basic and clinical research on PBC in China, with major contributions in diagnostic criteria, treatment, and on basic biology. This has led to exciting proposals based on Chinese PBC cohorts. SUMMARY: Chinese hepatologists and scientists are now focusing their efforts on PBC. These efforts have led to new diagnostic biomarkers, novel therapeutic methods (stem cells and Chinese traditional medicine), and unique immunological mechanisms, including roles for T-follicular helper cells and monocyte subpopulations, both of which are involved in the breach of immune tolerance for PBC.

AAV-IL-22 modifies liver chemokine activity and ameliorates portal inflammation in murine autoimmune cholangitis.

There remain significant obstacles in developing biologics to treat primary biliary cholangitis (PBC). Although a number of agents have been studied both in murine models and human patients, the results have been relatively disappointing. IL-22 is a member of the IL-10 family and has multiple theoretical reasons for predicting successful usage in PBC. We have taken advantage of an IL-22 expressing adeno-associated virus (AAV-IL-22) to address the potential role of IL-22 in not only protecting mice from autoimmune cholangitis, but also in treating animals with established portal inflammation. Using our established mouse model of 2-OA-OVA immunization, including α-galactosylceramide (α-GalCer) stimulation, we treated mice both before and after the onset of clinical disease with AAV-IL-22. Firstly, AAV-IL-22 treatment given prior to 2-OA-OVA and α-GalCer exposure, i.e. before the onset of disease, significantly reduces the portal inflammatory response, production of Th1 cytokines and appearance of liver fibrosis. It also reduced the liver lymphotropic chemokines CCL5, CCL19, CXCL9, and CXCL10. Secondly, and more importantly, therapeutic use of AAV-IL-22, administered after the onset of disease, achieved a greater hurdle and significantly improved portal pathology. Further the improvements in inflammation were negatively correlated with levels of CCL5 and CXCL10 and positively correlated with levels of IL-22. In conclusion, we submit that the clinical use of IL-22 has a potential role in modulating the inflammatory portal process in patients with PBC.

Failure of resolution of portal fibrosis during omega-3 fatty acid lipid emulsion therapy in two patients with irreversible intestinal failure.

Parenteral omega-3 fatty acid lipid emulsions have been evaluated for their potential role in reversing intestinal failure-associated liver disease. We report our experience using Omegaven in 2 patients with irreversible intestinal failure and intestinal failure-associated liver disease. Despite biochemical and histologic improvement in cholestasis, both patients had persisting, significant portal fibrosis on liver biopsy.

An integrated care pathway improves quality of life in Primary Biliary Cirrhosis.

BACKGROUND: Clinical management of the chronic autoimmune liver disease, Primary Biliary Cirrhosis (PBC) involves addressing the underlying liver disease and a range of symptoms independent of liver disease severity. We have formally explored how these two perspectives of chronic disease management can be combined into a clinic consultation and impact upon quality of life (QOL) in PBC. AIMS: To develop and implement the first Integrated Care Pathway (ICP) for the management of liver disease progression and symptom management in PBC. METHODS: Process mapping of current practice by a multidisciplinary group developed a flowchart of care from which the clinical record evolved. Symptom assessment is incorporated into the PBC ICP (QOL; PBC-40, autonomic symptoms; Orthostatic Grading Scale, daytime sleepiness; Epworth Sleepiness Scale). All patients were considered who attended clinic between July 2005 and June 2006. Symptom assessment was repeated after 1 year in those participating in the initial clinic cohort. RESULTS: The PBC ICP was successfully introduced into our clinical environment with high levels of patient satisfaction. A total of 225 PBC patients attended over 12 months. Initial QOL assessments were in 195 (87%). Five patients died (3%). Repeat assessment 1 year later occurred in 149 subjects (149/190; 78%). All symptom domains improved after ICP implementation with significant improvements in those with moderate and severe symptoms in all PBC-40 symptom domains (P < 0.02). In those with severe fatigue (n = 38) symptom improvement was even more dramatic (P = 0.002). CONCLUSION: ICP implementation delivers evidence-based care, leads to improvements in QOL coupled with high levels of patient satisfaction.

Intensive plasmapheresis as an alternative therapy for intractable pruritus of primary biliary cirrhosis.

Primary biliary cirrhosis is a chronic disease of presumed autoimmune etiology, generally associated with other systemic abnormalities such as scleroderma, characteristic of Sjogren's syndrome and Raynaud's syndrome, for which pruritus is the most troublesome symptom. Treatment of this disease is a major unsolved problem. Although the use of cholestyramine has been effective, a considerable number of cases are refractory to the drug and to other agents such as corticosteroids, azathioprine and penicillamine. Plasma exchange has proven to be a useful option in four female patients with primary biliary cirrhosis--two with grade III histology and the other two with grade IV disease and intractable pruritus. The procedure was well tolerated and no side effects were observed. There was a temporary but significant attenuation of pruritus and improvement of melanoderma. Intensive plasma exchange is proposed as an alternative therapy in primary biliary cirrhosis with refractory pruritus.

A combination of phototherapy and cholestyramine for the relief of pruritus in primary biliary cirrhosis.

A patient with primary biliary cirrhosis is reported in whom UV phototherapy alone was repeatedly effective in controlling severe pruritus. Symptomatic relief was sustained by introducing cholestyramine at a low dosage, despite previous failure of the drug alone to produce any therapeutic benefit, even in large doses. Bile acid concentrations were measured in sera, urine and suction blister fluid from skin exposed to ultraviolet light before, during and following treatment. The findings suggest that phototherapy reduces cutaneous bile acid levels which can subsequently be maintained by low dose cholestyramine. Routine liver function tests remained unaltered. This combination of phototherapy and cholestyramine may be useful in controlling severe pruritus in primary biliary cirrhosis when the drug alone is not tolerated or is ineffective.

Vitamin D metabolism in acute and chronic cholestasis.

To study the effects of acute and chronic cholestasis on vitamin D metabolism we investigated six cases of acute extrahepatic obstructive jaundice and eight cases of primary biliary cirrhosis (PBC) (three supplemented with vitamin D). Plasma 25-hydroxyvitamin D (25OHD) was low in the patients with PBC unsupplemented with vitamin D but normal in obstructive jaundice. None of the patients with PBC showed radiological or histological evidence of osteomalacia. In PBC, dietary intake of vitamin D was low but response to ultra-violet irradiation of the skin was normal even in those with a considerably raised serum bilirubin. Patients with PBC or obstructive jaundice had low levels of 25 hydroxyvitamin D binding protein which correlated with the serum albumin. The half-life of intravenously injected (3)H vitamin D(3) ((3)HD(3)) and the subsequent production of (3)H 25OHD were normal in all the patients with obstructive jaundice and in most with PBC. The two patients with PBC who produced less (3)H 25OHD than expected were receiving vitamin D supplements. The urinary tritium ((3)H) excretion after the injection of (3)HD(3) correlated with the serum bilirubin. After the injection of (3)H 25OHD(3) the urinary excretion of (3)H was minimal and did not correlate with the serum bilirubin, suggesting that the radioactivity appearing in the urine after the (3)H vitamin D(3) injection was associated with vitamin D metabolites other than 25OHD. Factors contributing to the low plasma 25OHD in primary biliary cirrhosis may be a low dietary intake of vitamin D, inadequate exposure to ultra-violet light, and a tendency to urinary wastage of vitamin D metabolites.